Platinum-binding peptides: understanding of selective binding and multifunctionality

Platinum-binding peptides have been used for fabrication of complex platinum nanomaterials such as catalysts, metallopharmaceuticals, and electrodes. In this review, we present understanding of the mechanisms behind platinum-binding (Pt-binding) peptides and the applications of the peptides as multifunctional biomaterials. We discuss how the surface recognition, the roles of individual amino acids, and arrangement of amino acid sequences interplay. Our summary on the current state of understanding of Pt-binding peptides highlights opportunities for interdisciplinary research which will expand the applicability of these multifunctional Pt-binding peptides.

Heterocyclic Moieties as HDAC Inhibitors: Role in Cancer Therapeutic

‘Epigenetic’ regulation of genes via post-translational modulation of proteins is a well explored approach for the disease therapies, particularly cancer chemotherapeutics. Histone deacetylases (HDACs) are one of the important epigenetic targets and are mainly responsible for balancing the acetylation/deacetylation of lysine amino acids on histone/nonhistone proteins along with histone acetyltransferase (HAT). HDAC inhibitors (HDACIs) have become an important biologically active compounds for the treatment of cancers due to cell cycle arrest, differentiation and apoptosis in tumor cells and thus leads to anticancer activity. Out of the four classes of HDAC i.e. Class I, II, III and IV, HDACIs act on Class-IV (Zinc dependent HDAC) and various FDA-approved drugs belong to this category. The required canonical pharmacophore model (zinc binding group, surface recognition cap and appropriate linker) supported by HDACIs, various heterocyclic moieties containing compounds exhibiting HDAC inhibitory activity and structure activity relationship of different synthetic derivatives reported during last twelve years have been summarized in this review.

Mobile Augmented Reality for Low-End Devices Based on Planar Surface Recognition and Optimized Vertex Data Rendering

Mobile Augmented Reality (MAR) is designed to keep pace with high-end mobile computing and their powerful sensors. This evolution excludes users with low-end devices and network constraints. This article presents ModAR, a hybrid Android prototype that expands the MAR experience to the aforementioned target group. It combines feature-based image matching and pose estimation with fast rendering of 3D textured models. Planar objects of the real environment are used as pattern images for overlaying users’ meshes or the app’s default ones. Since ModAR is based on the OpenCV C++ library at Android NDK and OpenGL ES 2.0 graphics API, there are no dependencies on additional software, operating system version or model-specific hardware. The developed 3D graphics engine implements optimized vertex-data rendering with a combination of data grouping, synchronization, sub-texture compression and instancing for limited CPU/GPU resources and a single-threaded approach. It achieves up to 3 × speed-up compared to standard index rendering, and AR overlay of a 50 K vertices 3D model in less than 30 s. Several deployment scenarios on pose estimation demonstrate that the oriented FAST detector with an upper threshold of features per frame combined with the ORB descriptor yield best results in terms of robustness and efficiency, achieving a 90% reduction of image matching time compared to the time required by the AGAST detector and the BRISK descriptor, corresponding to pattern recognition accuracy of above 90% for a wide range of scale changes, regardless of any in-plane rotations and partial occlusions of the pattern.

The Antagonist pGlu-βGlu-Pro-NH2 Binds to an Allosteric Site of the Thyrotropin-Releasing Hormone Receptor

After we identified pGlu-βGlu-Pro-NH2 as the first functional antagonist of the cholinergic central actions of the thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH2), we became interested in finding the receptor-associated mechanism responsible for this antagonism. By utilizing a human TRH receptor (hTRH-R) homology model, we first refined the active binding site within the transmembrane bundle of this receptor to enhance TRH’s binding affinity. However, this binding site did not accommodate the TRH antagonist. This prompted us to consider a potential allosteric binding site in the extracellular domain (ECD). Searches for ECD binding pockets prompted a remodeling of the extracellular loops and the N-terminus. We found that different trajectories of ECDs produced novel binding cavities that were then systematically probed with TRH, as well as its antagonist. This led us to establish not only a surface-recognition binding site for TRH, but also an allosteric site that exhibited a selective and high-affinity binding for pGlu-βGlu-Pro-NH2. The allosteric binding of this TRH antagonist is more robust than TRH’s binding to its own active site. The findings reported here may shed light on the mechanisms and the multimodal roles by which the ECD of a TRH receptor is involved in agonist and/or antagonist actions.

Optimal anchoring of a foldamer inhibitor of ASF1 histone chaperone through backbone plasticity

Sequence-specific oligomers with predictable folding patterns, i.e., foldamers, provide new opportunities to mimic α-helical peptides and design inhibitors of protein-protein interactions. One major hurdle of this strategy is to retain the correct orientation of key side chains involved in protein surface recognition. Here, we show that the structural plasticity of a foldamer backbone may notably contribute to the required spatial adjustment for optimal interaction with the protein surface. By using oligoureas as α helix mimics, we designed a foldamer/peptide hybrid inhibitor of histone chaperone ASF1, a key regulator of chromatin dynamics. The crystal structure of its complex with ASF1 reveals a notable plasticity of the urea backbone, which adapts to the ASF1 surface to maintain the same binding interface. One additional benefit of generating ASF1 ligands with nonpeptide oligourea segments is the resistance to proteolysis in human plasma, which was highly improved compared to the cognate α-helical peptide.